Although adolescent depression has been linked to individual chronic conditions, its broader role in shaping multimorbidity risk remains understudied.

A total of 87,562 UK Biobank participants were included, of whom 18,851 had documented adolescent depression. Cox proportional hazards models were applied to evaluate associations between adolescent depression and 24 chronic diseases, followed by stratified analyses by sex and age. Two-sample Mendelian randomization (MR) was then conducted to infer causality for diseases showing significant associations. Genomic colocalization analyses were performed using relevant GWAS data to identify shared causal variants. Mediation analyses were performed to detect possible mediating factors, including the frailty index, KDM biological age acceleration, allostatic load and 30 circulating biomarkers.

Adolescent depression was associated with elevated risk for 12 chronic diseases, with strongest associations for hypothyroidism (HR = 1.29 [1.18–1.42]), diabetes (HR = 1.25 [1.13–1.38]) and chronic obstructive pulmonary disease (COPD) (HR = 1.74 [1.50–2.01]). Risks were notably higher among females and younger adults. MR confirmed likely causal relationships for hypothyroidism (OR = 1.45 [1.03–2.05]), diabetes (OR = 1.01 [1.01–1.02]) and COPD (OR = 1.04 [1.02–1.06]). Genomic colocalization revealed a shared genetic signal at the CDSN/PSORS1C1 locus between adolescent depression and hypothyroidism. Mediation analyses revealed disease-specific pathways: creatinine for hypothyroidism, testosterone for diabetes, KDM biological ageing for COPD and frailty index across all three conditions.

Adolescent depression confers systemic vulnerability through genetic and metabolic mechanisms, with amplified risks in females and individuals aged ≤55 years. These findings support early, integrated interventions to mitigate long-term multimorbidity.

Nonsuicidal self-injury (NSSI) in adolescents with depressive disorder is characterized by recurrent impulsivity and is a predictor of future suicidal behavior, necessitating effective and feasible interventions. Mindfulness-based cognitive therapy for adolescents (MBCT-A), a first-line treatment for depression, was evaluated in this trial for its efficacy in reducing NSSI in this population.

In this randomized, single-blind, controlled trial, 94 hospitalized adolescents diagnosed with depressive disorder and engaging in NSSI were allocated to either MBCT-A plus treatment-as-usual (TAU) or TAU alone. The primary outcome was the severity of NSSI, measured by the Adolescent Self-Harm Scale (ASHS) at baseline, post treatment (4 weeks), and at 1-month follow-up. Secondary outcomes encompassed symptoms of anxiety, depression, emotion regulation, risk behaviors, life satisfaction, resilience, rumination, coping styles, and mindfulness. Both intention-to-treat (ITT) and per-protocol (PP) analyses were conducted.

Both ITT and PP analyses revealed significant between-group differences in NSSI severity at 4 weeks. Compared to the control group, the MBCT-A group showed significant improvements in mindfulness awareness, nonreactivity, emotional awareness, depressive symptoms, emotion regulation, and rumination (all P < 0.05). At the 1-month follow-up, the intervention group maintained a significant reduction in NSSI severity (interaction effect: F = 9.454, P < 0.001).

MBCT-A is effective in reducing NSSI behavior and improving mindfulness, emotion regulation, and depressive symptoms among adolescents with depressive disorder and NSSI. These findings support the clinical application of MBCT-A for this high-risk population.

Adolescence is a period marked by high vulnerability to onset of depression. Neuroimaging studies have revealed considerableatrophy of brain structure in patients with major depressive disorder (MDD). However, the causal structural networks underpinning gray matter atrophies in depressed adolescents remain unclear. This study aimed to examine the initial gray matter alterations in MDD adolescents and investigate their causal relationships of abnormalities within brain structural networks.

First-episode adolescent patients with MDD (n = 80, age = 15.57 ± 1.78) and age- and sex-matched healthy controls (n = 82, age = 16.11 ± 2.76) were included. We analyzed T1-weighted structural images using voxel-based morphometry to identify gray matter alterations in patients and the disease stage-specific abnormalities. Granger causality analysis was then conducted to construct causal structural covariance networks. We also identified potential pathways between the causal source and target.

Compared to controls, MDD patients with shorter illness duration showed gray matter atrophy in localized brain regions such as ventral medial prefrontal cortex (vmPFC), anterior cingulate cortex, and insula. With a prolonged course of MDD, gray matter atrophy extended to widespread brain areas. Causal network results demonstrated that early abnormalities had positive effects on the default mode, frontoparietal networks, and reward circuits. Moreover, vmPFC demonstrated the highest out-degree value, possibly representing the initial source of brain abnormality in adolescent depression.

These findings revealed the progression of gray matter atrophy in adolescent depression and demonstrated the directional influences between initial localized alterations and subsequent deterioration in widespread brain networks.

Hippocampal disruptions represent potential neuropathological biomarkers in depressed adolescents with cognitive dysfunctions. Given heterogeneous outcomes of whole-hippocampus analyses, we investigated subregional abnormalities in depressed adolescents and their associations with symptom severity and cognitive dysfunctions.

MethodsSeventy-nine first-episode depressive patients (ag = 15.54 ± 1.83) and 71 healthy controls (age = 16.18 ± 2.85) were included. All participants underwent T1 and T2 imaging, completed depressive severity assessments, and performed cognitive assessments on memory, emotional recognition, cognitive control, and attention. Freesurfer was used to segment each hippocampus into 12 subfields. Multivariable analyses of variance were performed to identify overall and disease severity-related abnormalities in patients. LASSO regression was also conducted to explore the associations between hippocampal subfields and patients’ cognitive abilities.

Depressed adolescents showed decreases in dentate gyrus, CA1, CA2/3, CA4, fimbria, tail, and molecular layer. Analyses of overall symptom severity, duration, self-harm behavior, and suicidality suggested that severity-related decreases mainly manifested in CA regions and involved surrounding subfields with disease severity increases. LASSO regression indicated that hippocampal subfield abnormalities had the strongest associations with memory impairments, with CA regions and dentate gyrus showing the highest weights.

Hippocampal abnormalities are widespread in depressed adolescents and such abnormalities may spread from CA regions to surrounding areas as the disease progresses. Abnormalities in CA regions and dentate gyrus among these subfields primarily link with memory impairments in patients. These results demonstrate that hippocampal subsections may serve as useful biomarkers of depression progression in adolescents, offering new directions for early clinical intervention.

Cognitive behavioural therapy (CBT) and medication are widely accepted and useful interventions for individuals with depression. However, a gap remains in our current understanding of how CBT directly benefits adolescents with depression.

The purpose of this study was to examine the short- and long-term effectiveness of CBT only, CBT+Medication, or Medication alone in reducing the duration of major depressive episodes, lessening internalizing and externalizing symptoms and improving global functioning.

Data were extracted from 14 unique studies with a total of 35 comparisons. Network meta-analysis was conducted and p-scores, a measure of the extent of certainty that one treatment is better than another, were used to rank treatments.

There was no significant difference between any two treatments for depression, nor internalizing or externalizing symptoms. For global functioning, CBT had significantly greater effect at the longest follow-up than CBT+Medication. CBT+Medication had the highest p-score for depression, short- and long-term effects, and internalizing and externalizing symptoms long-term effects. No indication of publication bias was found.

Neither modality, CBT nor medication, is superior for treating adolescent depression. However, CBT was superior in improving global functioning, which is essential for meeting developmental goals.

The relationships between offspring depression profiles across adolescence and different timings of parental depression during the perinatal period remain unknown.

To explore different timings of maternal and paternal perinatal depression in relation to patterns of change in offspring depressive mood over a 14 year period.

Data were obtained from the Avon Longitudinal Study of Parents and Children (ALSPAC). Parental antenatal depression (ANTD) was assessed at 18 weeks gestation, and postnatal depression (PNTD) at 8 weeks postpartum. Population-averaged trajectories of offspring depressive symptoms were estimated using the Short Mood and Feelings Questionnaire (SMFQ) on nine occasions between 10 and 24 years of age.

Full data were available for 5029 individuals. Offspring exposed to both timings of maternal depression had higher depressive symptoms across adolescence compared with offspring not exposed to ANTD or PNTD, characterised by higher depressive symptoms at age 16 (7.07 SMFQ points (95% CI = 6.19, 7.95; P < 0.001)) and a greater rate of linear change (0.698 SMFQ points (95% CI = 0.47, 0.93; P = 0.002)). Isolated maternal ANTD and to a lesser extent PNTD were also both associated with higher depressive symptoms at age 16, yet isolated maternal PNTD showed greater evidence for an increased rate of linear change across adolescence. A similar pattern was observed for paternal ANTD and PNTD, although effect sizes were attenuated.

This study adds to the literature demonstrating that exposure to two timings of maternal depression (ANTD and PNTD) is strongly associated with greater offspring trajectories of depressive symptoms.

Adolescent depression has been shown to have a range of adverse outcomes. We used longitudinal data to investigate subsequent higher education in former depressed adolescents.

A Swedish population-based investigation of depression in 16–17-year-olds was followed up in national registers 15 years later. Adolescents with depression (n = 361, 78% females) were compared to a group of non-depressed peers of the same age (n = 248, 77% females). The main outcome was graduation from higher education by age 30.

The adolescent with depression were less likely than their non-depressed peers to have graduated from higher education by age 30, both regarding females (27.7% vs. 36.4%, p < .05) and males (12.7% vs. 28.6%, p < .05). After adjustment for early school performance, socioeconomic status and maternal education, the decreased likelihood of subsequent graduation from higher education remained for depressed males (OR, 0.27; 95% CI, 0.08–0.93) but not for depressed females (OR, 0.93; 95% CI, 0.58–1.49).

Contrary to what previous research has suggested, adolescent depression and its consequences might be particularly destructive to subsequent higher education in males.

Mitochondrial dysfunction has been increasingly examined as a potential pathogenic event in psychiatric disorders, although its role early in the course of major depressive disorder (MDD) is unclear. Therefore, the purpose of this study was to investigate mitochondrial dysfunction in medication-free adolescents with MDD through in vivo measurements of neurometabolites using high-spatial resolution multislice/multivoxel proton magnetic resonance spectroscopy.

Twenty-three adolescents with MDD and 29 healthy controls, ages 12–20, were scanned at 3 T and concentrations of ventricular cerebrospinal fluid lactate, as well as N-acetyl-aspartate (NAA), total creatine (tCr), and total choline (tCho) in the bilateral caudate, putamen, and thalamus were reported.

Adolescents with MDD exhibited increased ventricular lactate compared to healthy controls [F(1,41) = 6.98, P = 0.01]. However, there were no group differences in the other neurometabolites. Dimensional analyses in the depressed group showed no relation between any of the neurometabolites and symptomatology, including anhedonia and fatigue.

Increased ventricular lactate in depressed adolescents suggests mitochondrial dysfunction may be present early in the course of MDD; however it is still not known whether the presence of mitochondrial dysfunction is a trait vulnerability of individuals predisposed to psychopathology or a state feature of the disorder. Therefore, there is a need for larger multimodal studies to clarify these chemical findings in the context of network function.

Fluoxetine is generally regarded as the first-line pharmacological treatment for young people, as it is believed to show a more favourable benefit:risk ratio than other antidepressants. However, the mechanisms through which fluoxetine influences symptoms in youth have been little investigated. This study examined whether acute administration of fluoxetine in a sample of young healthy adults altered the processing of affective information, including positive, sad and anger cues.

A total of 35 male and female volunteers aged between 18 and 21 years old were randomized to receive a single 20 mg dose of fluoxetine or placebo. At 6 h after administration, participants completed a facial expression recognition task, an emotion-potentiated startle task, an attentional dot-probe task and the Rapid Serial Visual Presentation. Subjective ratings of mood, anxiety and side effects were also taken pre- and post-fluoxetine/placebo administration.

Relative to placebo-treated participants, participants receiving fluoxetine were less accurate at identifying anger and sadness and did not show the emotion-potentiated startle effect. There were no overall significant effects of fluoxetine on subjective ratings of mood.

Fluoxetine can modulate emotional processing after a single dose in young adults. This pattern of effects suggests a potential cognitive mechanism for the greater benefit:risk ratio of fluoxetine in adolescent patients.